The ubiquitin-proteasome pathway is required for processing the NF-kappa B1 precursor protein and the activation of NF-kappa B

Cell. 1994 Sep 9;78(5):773-85. doi: 10.1016/s0092-8674(94)90482-0.


We demonstrate an essential role for the proteasome complex in two proteolytic processes required for activation of the transcription factor NF-kappa B. The p105 precursor of the p50 subunit of NF-kappa B is processed in vitro by an ATP-dependent process that requires proteasomes and ubiquitin conjugation. The C-terminal region of p105 is rapidly degraded, leaving the N-terminal p50 domain. p105 processing can be blocked in intact cells with inhibitors of the proteasome or in yeast with proteasome mutants. These inhibitors also block the activation of NF-kappa B and the rapid degradation of I kappa B alpha induced by tumor necrosis factor alpha. Thus, the ubiquitin-proteasome pathway functions not only in the complete degradation of polypeptides, but also in the regulated processing of precursors into active proteins.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Amino Acid Sequence
  • Animals
  • Cells, Cultured
  • Cysteine Endopeptidases / drug effects
  • Cysteine Endopeptidases / metabolism*
  • DNA-Binding Proteins / metabolism
  • Humans
  • I-kappa B Proteins*
  • Leupeptins / pharmacology
  • Models, Biological
  • Molecular Sequence Data
  • Multienzyme Complexes / drug effects
  • Multienzyme Complexes / metabolism*
  • NF-KappaB Inhibitor alpha
  • NF-kappa B / biosynthesis*
  • NF-kappa B / metabolism*
  • NF-kappa B p50 Subunit
  • Protease Inhibitors / pharmacology
  • Proteasome Endopeptidase Complex
  • Protein Precursors / metabolism*
  • Protein Processing, Post-Translational* / drug effects
  • Ubiquitins / metabolism*


  • DNA-Binding Proteins
  • I-kappa B Proteins
  • Leupeptins
  • Multienzyme Complexes
  • NF-kappa B
  • NF-kappa B p50 Subunit
  • NFKBIA protein, human
  • Protease Inhibitors
  • Protein Precursors
  • Ubiquitins
  • carbobenzoxy-leucyl-leucyl-norvalinal
  • acetylleucyl-leucyl-norleucinal
  • NF-KappaB Inhibitor alpha
  • Adenosine Triphosphate
  • Cysteine Endopeptidases
  • Proteasome Endopeptidase Complex
  • benzyloxycarbonylleucyl-leucyl-leucine aldehyde